Evaluation of Fatty Acid Synthase as a Molecular Target for Stress-Dependent Fungicidal Activity of 1-Geranylgeranylpyridinium

Akira Ogita; Takeshi Doi; Shintaro Miyuki; Yoshinosuke Usuki; Yoshihiro Yamaguchi; Ken-ichi Fujita

Evaluation of Fatty Acid Synthase as a Molecular Target for Stress-Dependent Fungicidal Activity of 1-Geranylgeranylpyridinium

Akira Ogita * §

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Takeshi Doi

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Shintaro Miyuki

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Yoshinosuke Usuki

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Yoshihiro Yamaguchi

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Ken-ichi Fujita

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Osaka City University

Evaluation of Fatty Acid Synthase as a Molecular Target for Stress-Dependent Fungicidal Activity of 1-Geranylgeranylpyridinium

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Abstract

Among various isoprenoid compounds, 1-geranylgeranylpyridinium (GGPy) showed remarkable lethal effects on Saccharomyces cerevisiae cells similarly under hypo-and hyperosmotic conditions at 30ºC. In addition to such osmotic stress, GGPy exhibited temperature-dependent lethal effects against S. cerevisiae and the pathogenic yeast Candida albicans at the human body temperature of 37ºC. Fatty acid synthase (FAS) was identified as one of the GGPy-binding proteins and was considered a molecular target of GGPy in its inhibitory effect on the fungal stress adaptation. GGPy was not inhibitory to the activity of FAS assayed upon NADPH oxidation involved in acyl chain elongation by this multi-functional enzyme complex. Nevertheless, the lethality of GGPy was repressed in the medium where polyoxyethylene sorbitan monopalmitate (Tween 40) supplemented as the water-soluble and esterasedependent source of palmitic acid. These findings may suggest that GGPy is permissive for acetyl unit incorporation into the growing chain of fatty acyl-CoA by FAS butis restrictive to its ultimate elongation to palmitoyl-CoA as a donor of the long-chain saturated fatty acid for the synthesis of stress-tolerant glycerophospholipids.

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Funding

No external funding was declared for this work.

Conflict of Interest

The authors declare no conflict of interest.

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How to Cite This Article

Akira Ogita, Takeshi Doi, Shintaro Miyuki, Yoshinosuke Usuki, Yoshihiro Yamaguchi, Ken-ichi Fujita. 2020. "Evaluation of Fatty Acid Synthase as a Molecular Target for Stress-Dependent Fungicidal Activity of 1-Geranylgeranylpyridinium". Global Journal of Medical Research, Global Journal of Medical Research - K: Interdisciplinary GJMR-K Volume 20 (GJMR Volume 20 Issue K2).

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GJMR Volume 20 Issue K2

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Journal Specifications

Crossref Journal DOI 10.17406/gjmr

Print ISSN 0975-5888

e-ISSN 2249-4618

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Classification

GJMR-K Classification NLMC Code: WD 730

Submission ReceivedDecember 6, 2019
Peer Review Double Blind
Handling Editor
Accepted December 31, 2019
Published January 15, 2020

Version of record

v1.2

Issue date

March 19, 2020

Language

English

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